@article{wall_dyment_bodle_volmer_loboa_cederlund_fox_banes_2016, title={Cell signaling in tenocytes: Response to load and ligands in health and disease}, volume={920}, journal={Metabolic influences on risk for tendon disorders}, author={Wall, M. E. and Dyment, N. A. and Bodle, J. and Volmer, J. and Loboa, E. and Cederlund, A. and Fox, A. M. and Banes, A. J.}, year={2016}, pages={79–95} } @article{lavagnino_wall_little_banes_guilak_arnoczky_2015, title={Tendon mechanobiology: Current knowledge and future research opportunities}, volume={33}, number={6}, journal={Journal of Orthopaedic Research}, author={Lavagnino, M. and Wall, M. E. and Little, D. and Banes, A. J. and Guilak, F. and Arnoczky, S. P.}, year={2015}, pages={813–822} } @article{banes_2013, title={Out of academics: education, entrepreneurship and enterprise}, volume={41}, number={9}, journal={Annals of Biomedical Engineering}, author={Banes, A. J.}, year={2013}, pages={1926–1938} } @article{qi_chi_bynum_banes_2011, title={Gap junctions in IL-1 beta-mediated cell survival response to strain}, volume={110}, number={5}, journal={Journal of Applied Physiology}, author={Qi, J. and Chi, L. Q. and Bynum, D. and Banes, A. J.}, year={2011}, pages={1425–1431} } @article{qi_chi_wang_sumanasinghe_wall_tsuzaki_banes_2009, title={Modulation of collagen gel compaction by extracellular ATP is MAPK and NF-kappa B pathways dependent}, volume={315}, ISSN={["0014-4827"]}, DOI={10.1016/j.yexcr.2009.02.012}, abstractNote={Understanding the mechanisms that regulate mechanosensitivity in osteoblasts is important for controlling bone homeostasis and the development of new drugs to combat bone loss. It is believed that prestress or force generation (the tensile stress within the cell body) plays an important role in regulating cellular mechanosensitivity. In the present study, a three-dimensional (3D) collagen culture was used to monitor the change in prestress of the osteoblast-like cells. Collagen hydrogel compaction has been used as an indicator of the change in the degree of cell prestress. Previous results in this model demonstrated that extracellular ATP reduced the mechanosensitivity of osteoblasts by reducing cellular prestress. To elucidate the potential mechanisms involved in this process, the signaling pathways downstream of P2 purinoceptors involved in regulating the compaction of type I collagen gels were investigated. By using specific inhibitors to these signaling pathways, we found that ATP-induced reduction in collagen gel compaction rate is dependent on mitogen-activated protein kinase (MAKP) and NF-kappaB pathways. However, blocking protein kinase C with GF109203X did not change the compaction kinetics in the presence of ATPgammaS. Moreover, blocking cyclic AMP (cAMP), phosphatidylinositol-3 kinase (PI3K), calmodulin (CaM) or L-type voltage sensitive calcium channels did not affect ATP's ability to reduce collagen gel compaction. The results from the present and previous studies indicate that extracellular ATP may act as a negative feedback modulator in the mechanotransduction system since mechanical stimuli increase ATP release from stimulated cells.}, number={11}, journal={EXPERIMENTAL CELL RESEARCH}, author={Qi, Jie and Chi, Liqun and Wang, Jian and Sumanasinghe, Ruwan and Wall, Michelle and Tsuzaki, Mari and Banes, Albert J.}, year={2009}, month={Jul}, pages={1990–2000} } @article{hanson_marvel_bernacki_banes_aalst_loboa_2009, title={Osteogenic Effects of Rest Inserted and Continuous Cyclic Tensile Strain on hASC Lines with Disparate Osteodifferentiation Capabilities}, volume={37}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-009-9648-7}, abstractNote={We investigated the effects of two types of cyclic tensile strain, continuous and rest inserted, on osteogenic differentiation of human adipose-derived adult stem cells (hASCs). The influence of these mechanical strains was tested on two hASC lines having different mineral deposition potential, with one cell line depositing approximately nine times as much calcium as the other hASC line after 14 days of culture in osteogenic medium on tissue culture plastic. Results showed that both continuous (10% strain, 1 Hz) and rest inserted cyclic tensile strain (10% strain, 1 Hz, 10 s rest after each cycle) regimens increased the amount and rate of calcium deposition for both high and low calcium depositing hASC lines as compared to unstrained controls. The response was similar for both types of tensile strain for a given cell line, however, cyclic tensile strain had a much stronger osteogenic effect on the high calcium depositing hASC line, suggesting that mechanical loading has a greater effect on cell lines that already have an innate ability to produce bone as compared to cell lines that do not. This is the first study to investigate the osteodifferentiation effects of cyclic tensile strain on hASCs and the first to show that both continuous (10%, 1 Hz) and rest inserted (10%, 1 Hz, 10 s rest) cyclic tensile strain accelerate hASC osteodifferentiation and increase calcium accretion.}, number={5}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Hanson, Ariel D. and Marvel, Skylar W. and Bernacki, Susan H. and Banes, Albert J. and Aalst, John and Loboa, Elizabeth G.}, year={2009}, month={May}, pages={955–965} } @article{qi_chi_labeit_banes_2008, title={Nuclear localization of the titin Z1Z2Zr domain and role in regulating cell proliferation}, volume={295}, ISSN={["1522-1563"]}, DOI={10.1152/ajpcell.90619.2007}, abstractNote={Titin (also called connectin) is a major protein in sarcomere assembly as well as providing elastic return of the sarcomere postcontraction in cardiac and striated skeletal muscle tissues. In addition, it has been speculated that titin is associated with nuclear functions, including chromosome and spindle formation, and regulation of muscle gene expression. In the present study, a short isoform of titin was detected in a human osteoblastic cell line, MG-63 cells, by both immunostaining and Western blot analysis. Confocal images of titin staining showed both cytoplasmic and nuclear localization in a punctate pattern. Therefore, we hypothesized that human titin may contain a nuclear localization signal (NLS). A functional NLS, 200-PAKKTKT-206, located in a low-complexity, titin-specific region between Z2 and Z repeats, was found by sequentially deleting segments of the NH2-terminal sequence in conjunction with an enhanced green fluorescent protein reporter system and confirmed by site-directed mutagenesis. Overexpression of titin's amino terminal fragment (Z1Z2Zr) in human osteoblasts (MG-63) increased cell proliferation by activating the Wnt/β-catenin pathway. RT-PCR screens of tissue panels demonstrated that residues 1–206 were ubiquitously expressed at low levels in all tissues and cell types analyzed. Our data implicate a dual role for titin's amino terminal region, i.e., a novel nuclear function promoting cell division in addition to its known structural role in Z-line assembly.}, number={4}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY}, author={Qi, Jie and Chi, Liqun and Labeit, Siegfried and Banes, Albert J.}, year={2008}, month={Oct}, pages={C975–C985} } @article{devkota_tsuzaki_almekinders_banes_weinhold_2007, title={Distributing a fixed amount of cyclic loading to tendon explants over longer periods induces greater cellular and mechanical responses}, volume={25}, ISSN={["1554-527X"]}, DOI={10.1002/jor.20389}, abstractNote={AbstractTendon overuse injuries are a major source of clinical concern. Cyclic loading causes material damage and induces biochemical responses in tendon. The purpose of this study was to examine the biochemical and biomechanical tendon response after applying cyclical loading over varying durations. Avian flexor digitorum profundus tendons were loaded (3 or 12 MPa) to a fixed number of cycles across either 1 or 12 days in vitro. The tendon response evaluations included biomechanical data gathered during loading and subsequent failure testing. Evaluations also included cellular viability, cell death, and proteoglycan, collagen, collagenase, and prostaglandin E2 (PGE2) content measurements obtained from tissue specimens and media samples. Significant strains (up to 2%) accumulated during loading. Loading to 12 MPa significantly reduced maximum stress (33% and 27%) and energy density (42% and 50%) when applied across 1 or 12 days, respectively. Loading to 3 MPa also caused a 40% reduction in energy density, but only when applied across 12 days. Cell death and collagenase activity increased significantly with increasing magnitude and duration. However, no differences occurred in cell viability or collagen content. Glycosaminoglycan content increased 50% with load magnitude, while PGE2 production increased 2.5‐fold with loading magnitude and 11‐fold with increased duration. Mechanical fatigue‐induced mechanical property changes were exhibited by the tendons in response to increased loading magnitude across just 1 day. However, when the same loading was applied over a longer period, most outcomes were magnified substantially, relative to the short duration regimens. This is presumably due to the increased response time for the complex cellular response to loading. A key contributor may be the inflammatory mediator, PGE2, which exhibited large magnitude and duration dependent increases to cyclic loading. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1078–1086, 2007}, number={8}, journal={JOURNAL OF ORTHOPAEDIC RESEARCH}, author={Devkota, Aaditya C. and Tsuzaki, Mari and Almekinders, Louis C. and Banes, Albert J. and Weinhold, Paul S.}, year={2007}, month={Aug}, pages={1078–1086} } @article{qi_chi_faber_koller_banes_2007, title={ATP reduces gel compaction in osteoblast-populated collagen gels}, volume={102}, ISSN={["1522-1601"]}, DOI={10.1152/japplphysiol.00535.2006}, abstractNote={Bone remodeling is a localized process, but regulated by systemic signals such as hormones, cytokines, and mechanical loading. The mechanism by which bone cells convert these systemic signals into local signals is not completely understood. It is broadly accepted that the “prestress” in cytoskeleton of cells affects the magnitude of cellular responses to mechanical stimuli. Prestress derives from stiff cytoskeletal proteins and their connections within the cell and from cell contractility upon attaching to matrix. In an in vitro model of three-dimensional gel compaction, the relative cellular prestress levels in the same matrix environment were determined by matrix compaction rate: a greater compaction rate resulted in a higher level of prestress. In the present study, the effects of ATP on the prestress of osteoblasts were studied using mouse MC3T3-E1 cells grown in three-dimensional bioartificial tissues (BATs). ATP (≥100 μM) reduced the compaction rate of BATs in a dose-dependent manner. ADP, 2′-(or 3′)- O-(4-benzoylbenzoyl) ATP, and UTP, but not α,β-methylene ATP, also reduced the compaction rate but to a lesser extent. Pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid tetrasodium did not block the effect of ATP on BAT compaction rate. These results indicate that both P2X and P2Y receptors are involved in ATP-induced reduction of BAT compaction rate. Steady fluid flow and RT-PCR results showed that ATP reduced cell attachment on type I collagen by downregulating the expression of integrin α1. These results suggest a potential role for P2 receptors in matrix remodeling and repair and as a potential drug target in treatment of bone diseases.}, number={3}, journal={JOURNAL OF APPLIED PHYSIOLOGY}, author={Qi, Jie and Chi, Liqun and Faber, James and Koller, Beverly and Banes, Albert J.}, year={2007}, month={Mar}, pages={1152–1160} } @article{wall_otey_qi_banes_2007, title={Connexin 43 is localized with actin in tenocytes}, volume={64}, ISSN={["0886-1544"]}, DOI={10.1002/cm.20170}, abstractNote={AbstractVarieties of cell–matrix or cell–cell adhesions are associated with the actin cytoskeleton. However, for gap junctions, which are both channels and adhesions, there has been little evidence for such an association. The purpose of this study was to determine if connexin 43 (Cx43) associates with actin and to determine if this association is altered under mechanical load in tenocytes, a mechanically sensitive cell. Avian tenocytes were subjected to multiple cyclic strain regimens and then fixed and examined immunohistochemically at various times poststrain to determine where Cx43 protein was localized within the cells in relation to actin filaments. Four percent of tenocytes had colocalization of actin filaments and Cx43, which was significantly increased with 5% cyclic strain. To confirm this phenomenon, human tenocytes and COS‐7 cells were also subjected to cyclic strain and then fixed at the same times after strain. As with avian tenocytes, Cx43 was colocalized with actin in human tenocytes and COS‐7 cells. The colocalization increased significantly after cyclic strain in human tenocytes but not in COS‐7 cells. The lack of detectable changes in COS‐7 cells may indicate that they are less mechanosensitive than tenocytes perhaps due to the less robust actin cytoskeleton seen in the COS‐7 cells when compared to the tenocytes. Furthermore, inhibiting myosin II activity greatly reduced the immunohistochemically‐detectable Cx43 on actin filaments. Connexins may associate with actin to stabilize gap junctions at the plasma membrane, ensuring that tenocytes remain coupled during periods of prolonged or intense mechanical loading. Cell Motil. Cytoskeleton 2007. © 2006 Wiley‐Liss, Inc.}, number={2}, journal={CELL MOTILITY AND THE CYTOSKELETON}, author={Wall, Michelle E. and Otey, Carol and Qi, Jie and Banes, Albert J.}, year={2007}, month={Feb}, pages={121–130} } @article{qi_fox_alexopoulos_chi_bynum_guilak_banes_2006, title={IL-1 beta decreases the elastic modulus of human tenocytes}, volume={101}, ISSN={["1522-1601"]}, DOI={10.1152/japplphysiol.01128.2005}, abstractNote={ Cellular responses to mechanical stimuli are regulated by interactions with the extracellular matrix, which, in turn, are strongly influenced by the degree of cell stiffness (Young's modulus). It was hypothesized that a more elastic cell could better withstand the rigors of remodeling and mechanical loading. It was further hypothesized that interleukin-1β (IL-1β) would modulate intracellular cytoskeleton polymerization and regulate cell stiffness. The purpose of this study was to investigate the utility of IL-1β to alter the Young's modulus of human tenocytes. Young's modulus is the ratio of the stress to the strain, E = stress/strain = (F/ A)/(Δ L/ L0), where L0 is the equilibrium length, Δ L is the length change under the applied stress, F is the force applied, and A is the area over which the force is applied. Human tenocytes were incubated with 100 pM recombinant human IL-1β for 5 days. The Young's modulus was reduced by 27–63%. Actin filaments were disrupted in >75% of IL-1β-treated cells, resulting in a stellate shape. In contrast, immunostaining of α-tubulin showed increased intensity in IL-1β-treated tenocytes. Human tenocytes in IL-1β-treated bioartificial tendons were more tolerant to mechanical loading than were untreated counterparts. These results indicate that IL-1β reduced the Young's modulus of human tenocytes by disrupting the cytoskeleton and/or downregulating the expression of actin and upregulating the expression of tubulins. The reduction in cell modulus may help cells to survive excessive mechanical loading that may occur in damaged or healing tendons. }, number={1}, journal={JOURNAL OF APPLIED PHYSIOLOGY}, author={Qi, Jie and Fox, Ann Marie and Alexopoulos, Leonidas G. and Chi, Liqun and Bynum, Donald and Guilak, Farshid and Banes, Albert J.}, year={2006}, month={Jul}, pages={189–195} }